title: The SIN kinase Sid2 regulates cytoplasmic retention of the S. pombe Cdc14-like phosphatase Clp1.
abstract: Cdc14-family phosphatases play a conserved role in promoting mitotic exit and cytokinesis by dephosphorylating substrates of cyclin-dependent kinase (Cdk). Cdc14-family phosphatases have been best studied in yeast (for review, see [1, 2]), where budding yeast Cdc14 and its fission yeast homolog Clp1 are regulated partly by their localization; both proteins are thought to be sequestered in the nucleolus in interphase. Cdc14 and Clp1 are released from the nucleolus in mitosis, and in late mitosis conserved signaling pathways termed the mitotic exit network (MEN) and the septation initiation network (SIN) keeps Cdc14 and Clp1, respectively, out of the nucleolus through an unknown mechanism [3-6]. Here we show that the most downstream SIN component, the Ndr-family kinase Sid2, maintains Clp1 in the cytoplasm in late mitosis by phosphorylating Clp1 directly and thereby creating binding sites for the 14-3-3 protein Rad24. Mutation of the Sid2 phosphorylation sites on Clp1 disrupts the Clp1-Rad24 interaction and causes Clp1 to return prematurely to the nucleolus during cytokinesis. Loss of Clp1 from the cytoplasm in telophase renders cells sensitive to perturbation of the actomyosin ring but does not affect other Clp1 functions. Because all components of this pathway are conserved, this might be a broadly conserved mechanism for regulation of Cdc14-family phosphatases.
authors.affiliation: Department of Molecular Genetics and Microbiology and Interdisciplinary Graduate Program, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Chun-Ti
authors.initials: CT
authors.lastname: Chen
authors.forename: Anna
authors.initials: A
authors.lastname: Feoktistova
authors.forename: Jun-Song
authors.initials: JS
authors.lastname: Chen
authors.forename: Young-Sam
authors.initials: YS
authors.lastname: Shim
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Clifford
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Gould
authors.forename: Dannel
authors.initials: D
authors.lastname: McCollum
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002466:Cell Nucleolus / Q000378:metabolism; D048749:Cytokinesis; D003593:Cytoplasm / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029702:Schizosaccharomyces pombe Proteins; C501114:rad24 protein, S pombe; D011494:Protein Kinases; C113816:Sid2 protein, S pombe; C439269:Clp1 protein, S. pombe; D017027:Protein Tyrosine Phosphatases